| Identification | Back Directory | [Name]
Batefenterol | [CAS]
743461-65-6 | [Synonyms]
Batefenterol
GSK-961081,Batefenterol
Batefenterol(GSK961081)
GSK-961081(Batefenterol/TD-5959)
GSK961081;GSK-961081;GSK 961081;TD-5959;TD 5959;TD5959;BATEFENTEROL
Batefenterol, 98%, a novel muscarinic receptor antagonist and β2-adrenoceptor agonist
(R)-1-(3-((2-Chloro-4-(((2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)methyl)-5-methoxyphenyl)amino)-3-oxopropyl)piperidin-4-yl [1,1'-biphenyl]-2-ylcarbamate
Carbamic acid, N-[1,1'-biphenyl]-2-yl-, 1-[3-[[2-chloro-4-[[[(2R)-2-(1,2-dihydro-8-hydroxy-2-oxo-5-quinolinyl)-2-hydroxyethyl]amino]methyl]-5-methoxyphenyl]amino]-3-oxopropyl]-4-piperidinyl ester | [Molecular Formula]
C40H42ClN5O7 | [MDL Number]
MFCD27987925 | [MOL File]
743461-65-6.mol | [Molecular Weight]
740.24 |
| Chemical Properties | Back Directory | [Boiling point ]
948.3±65.0 °C(Predicted) | [density ]
1.41±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO:67.0(Max Conc. mg/mL);90.51(Max Conc. mM) | [form ]
A crystalline solid | [pka]
8.89±0.20(Predicted) | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Uses]
Batefenterol (GSK961081;TD-5959) is a novel muscarinic receptor antagonist and β2-adrenoceptor agonist; displays high affinity for hM2, hM3 muscarinic and hβ2-adrenoceptor with Ki values of 1.4, 1.3 and 3.7 nM, respectively. | [in vivo]
In the guinea pig bronchoprotection assay, inhaled Batefenterol produces potent, dose-dependent inhibition of bronchoconstrictor responses via MA (ED50=33.9 μg/mL), BA (ED50=14.1 μg/mL), and MABA (ED50=6.4 μg/mL) mechanisms. Significant bronchoprotective effects of Batefenterol are evident in guinea pigs via MA, BA, and MABA mechanisms for up to 7 days after dosing[1]. In guinea pig isolated trachea expressing native muscarinic M3 and β2, batefenterol produces smooth muscle relaxation through a dual mechanism involving competitive antagonism of the M3 receptor (EC50=50 nM) and agonism of the β2 receptor (EC50=25 nM). The combined effect on both muscarinic receptors and β2 receptors is more potent than either function working alone (EC50=10 nM). Batefenterol exhibits a rapid rate of clearance and short half-life[2]. | [IC 50]
mAChR2; mAChR3 | [storage]
Store at -20°C | [References]
[1] Hegde SS, et al. Pharmacologic characterization of GSK-961081 (TD-5959), a first-in-class inhaled bifunctional bronchodilator possessing muscarinic receptor antagonist and β2-adrenoceptor agonist properties. J Pharmacol Exp Ther. 2014 Oct;351(1):190-9. DOI:10.1124/jpet.114.216861
[2] Hughes AD, et al. Discovery of (R)-1-(3-((2-chloro-4-(((2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)methyl)-5-methoxyphenyl)amino)-3-oxopropyl)piperidin-4-yl [1,1'-biphenyl]-2-ylcarbamate (TD-5959, GSK961081, batefenterol): first-in-class dual pharmacology multivalent muscarinic antagonist and β? agonist (MABA) for the treatment of chronic obstructive pulmonary disease (COPD). J Med Chem. 2015 Mar 26;58(6):2609-22. DOI:10.1021/jm501915g |
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